Dystrophic forms of epidermolysis bullosa (EB) include an acquired type of EB (EBA) and two genetic types, dominant (DDEB) and recessive (RDEB). These patients all have chronic blistering and scarring diseases of the skin that may look clinically similar. The blisters are due to a separation at the basement membrane zone between the epidermis and dermis of skin and are associated with a lack of anchoring fibrils, structures made of type VII collagen (i.e., "the EBA antigen"), thought to be critical for epidermal-dermal cohesion. In EBA, anchoring fibril collagen is the target for autoantibodies, while autoantibodies do not play a role in genetic EB. Although the etiologies of these 3 diseases are almost certainly different, we hypothesize that each disease is characterized by abnormalities in type VII collagen. We further hypothesize that in EBA, the abnormal type VII collagen elicits an autoimmune response, while in DDEB and RDEB, the molecules form structurally unstable anchoring fibrils. We plan to characterize the type VII collagen in EB patients and normal individuals at the both the protein and genetic level. Using our cDNA probes for type VII (anchoring fibril) collagen, we will determine the antigenic epitopes of the molecule, characterize the nucleic acid and amino acid sequences of the full-length molecule, determine the genomic organization of the molecule, determine the expression of the molecule by keratinocytes derived from normal individuals and EB patients at the protein and mRNA level and in response to tretinoin and anti-sense oligonucleotides, and characterize the putative structural alterations in type VII collagen using amino acid and cDNA sequencing.